Cortical implants possess tremendous research and therapeutic importance. Man-made devices are being developed to be placed in the brain to restore function, treat neurological disease or monitor the physiological environment. A common problem faced by devices used in these applications is the lack of brain tissue biocompatibility. Within the scope of this project, attention is focused on the development of neural recording electrode arrays used in brain-machine interface studies, in which motor signals recorded from these electrodes can be used to control an external machine, a technology that can potentially restore movement to the paralyzed. However, the current unsatisfactory chronic performance of these devices has greatly hindered their clinical translation. The implanted electrodes cause progressive brain tissue responses including neuronal loss and inflammatory gliosis, which may lead to signal loss. We hypothesize that promoting neuronal health around the implant and reducing chronic inflammation may improve the quality, reliability and longevity of chronic recording. To test these hypotheses we developed two unique biomaterial strategies. One is surface immobilization of brain-derived biomolecules on the implant to provide bioactive sites for host tissue to interact with in a less invasive manner. The other strategy is an electrically controlled drug release system that can release anti-inflammatory drugs directly from the electrode surface to modulate the inflammatory tissue response. First we will respectively characterize the effect of these two approaches on modifying the tissue responses around the implanted electrodes, and determine to what degree promoted neuronal health and reduced inflammation influence the chronic recording performance. After the assessment is completed, the surface modification and controlled drug release approaches will be systematically combined to investigate whether there is a synergistic effect on the improvement of tissue- implant interface and chronic recording. Our specific aims are 1) To determine the effect of promoted neuronal survival and health on chronic recording quality, longevity and reliability. 2) To investigate the role of inflammation on chronic recording quality, longevity and reliability. 3) To evaluate the effect of combined treatment of surface modification and drug release on chronic recording quality, longevity and reliability. As shown above, the proposed project has both basic research and applied objectives. Chronic recording improvement is our immediate application-driven goal. However, the fundamental understanding of brain tissue response to implants and how different biomaterial strategies may modulate these responses are critically important for all types of neural implants, including neural recording devices, stimulators, CNS drug delivery systems and biochemical sensors. PUBLIC HEALTH RELEVANCE: Man-made devices are being developed to be placed in the brain to restore function and treat neurological disease. The goal of this project is to investigate the novel approaches that can be taken to make the implanted device more brain friendly and thereby obtain improved performance longevity and reliability.